Porphyromonas gingivalis is strongly associated with adult periodontitis, a widespread and costly disease that is primarily manifest in the oral cavity but also associated with systemic diseases such as atherosclerosis and rheumatoid arthritis. The adherence of P. gingivalis to commensal organisms such as Streptococcus gordonii facilitates the initial colonization of the oral cavity by P. gingivalis and our prior work identifed a peptide that potently inhibits this interaction. The main goal of this application is to develop ne nanoparticle (NP) delivery vehicles that will deliver high localized concentrations of the peptide for prolonged periods of time to sites in the oral cavity that are colonized by P. gingivalis. Two approaches will be used. Aim 1 will generate NPs that are surface?modified with the peptide in order increase effectiveness of the peptide by facilitating multi?valent interactions with P. gingivalis. The potency of the modified NPs will be compared to soluble peptide using established in vitro biofilm models and an in vivo animal model of periodontitis. In Aim 2, we will initially synthesize sustained release NPs that encapsulate the peptide. The load and release properties of the NPs will be optimized such that NPs will release an inhibitory concentration of the peptide for at least 24 hrs. Once NPs with the desired release properties are obtained, they will be surface modified with the CafA protein which mediates co?aggregation of Actinomyces with S. gordonii. The efficiency of NP adherence to streptococci will be determined and the function of sustained release NPs will be assessed using both in vitro biofilm models and a mouse model of periodontitis. It is anticipated that by targeting sustained release NPs to streptococci, the peptide will be delivered and released into a niche in the oral biofilm that is normally occupied by P. gingivalis, thus increasing the effectiveness of the peptide inhibitor.